Soluble FLT-1 in angiogenesis: pathophysiological roles and therapeutic implications

IF 9.2 1区 医学 Q1 PERIPHERAL VASCULAR DISEASE Angiogenesis Pub Date : 2024-08-29 DOI:10.1007/s10456-024-09942-8
Layal EI Wazan, Ariel Widhibrata, Guei-Sheung Liu
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Abstract

Fine-tuning angiogenesis, the development of new blood vessels, is essential for maintaining a healthy circulatory and lymphatic system. The small glycoprotein vascular endothelial growth factors (VEGF) are the key mediators in this process, binding to their corresponding membrane-bound VEGF receptors (VEGFRs) to activate angiogenesis signaling pathways. These pathways are crucial throughout human life as they are involved in lymphatic and vascular endothelial cell permeability, migration, proliferation, and survival. Neovascularization, the formation of abnormal blood vessels, occurs when there is a dysregulation of angiogenesis and can result in debilitating disease. Hence, VEGFRs have been widely studied to understand their role in disease-causing angiogenesis. VEGFR1, also known as Fms-like tyrosine kinase-1 (FLT-1), is also found in a soluble form, soluble FLT-1 or sFLT-1, which is known to act as a VEGF neutralizer. It is incorporated into anti-VEGF therapy, designed to treat diseases caused by neovascularization. Here we review the journey of sFLT-1 discovery and delve into the alternative splicing mechanism that creates the soluble receptor, its prevalence in disease states, and its use in current and future potential therapies.

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血管生成中的可溶性 FLT-1:病理生理学作用和治疗意义。
微调血管生成(新血管的发育)对于维持健康的循环和淋巴系统至关重要。小糖蛋白血管内皮生长因子(VEGF)是这一过程的关键介质,它与相应的膜结合血管内皮生长因子受体(VEGFR)结合,激活血管生成信号通路。这些途径对人的一生都至关重要,因为它们参与淋巴和血管内皮细胞的通透性、迁移、增殖和存活。当血管生成失调时,就会出现血管新生,即异常血管的形成,并可能导致衰弱性疾病。因此,人们对血管内皮生长因子受体(VEGFR)进行了广泛研究,以了解它们在致病血管生成中的作用。VEGFR1又称Fms样酪氨酸激酶-1(FLT-1),也以可溶性形式存在,即可溶性FLT-1或sFLT-1。它被纳入抗血管内皮生长因子疗法,旨在治疗由新生血管引起的疾病。在此,我们回顾了发现 sFLT-1 的历程,并深入探讨了产生可溶性受体的替代剪接机制、其在疾病状态中的普遍性及其在当前和未来潜在疗法中的应用。
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来源期刊
Angiogenesis
Angiogenesis PERIPHERAL VASCULAR DISEASE-
CiteScore
21.90
自引率
8.20%
发文量
37
审稿时长
6-12 weeks
期刊介绍: Angiogenesis, a renowned international journal, seeks to publish high-quality original articles and reviews on the cellular and molecular mechanisms governing angiogenesis in both normal and pathological conditions. By serving as a primary platform for swift communication within the field of angiogenesis research, this multidisciplinary journal showcases pioneering experimental studies utilizing molecular techniques, in vitro methods, animal models, and clinical investigations into angiogenic diseases. Furthermore, Angiogenesis sheds light on cutting-edge therapeutic strategies for promoting or inhibiting angiogenesis, while also highlighting fresh markers and techniques for disease diagnosis and prognosis.
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